The overall aim of the proposal is to conduct a prospective cohort study to determine and quantify the independent contribution of periodontal infections to the risk of atherosclerosis and vascular disease in a tri-ethnic population. Seizing the opportunity of the initiation of a larger cohort of stroke incidence in a community of Northern Manhattan where Blacks, Whites and Hispanics live together, and utilize the same health care facilities, we have assembled a multidisciplinary team of investigators in the fields of dentistry, medicine, and public health. 1,050 patients will be randomly selected from the community for the first 18 months of the study and followed over a period of 3 years. At baseline, they will undergo a comprehensive periodontal examination assessing clinical, radiologic, microbiologic (species specific DNA probes), immunologic (species-specific antibodies to periodontal pathogens) and inflammatory (GCF cytokine levels and systematic C-reactive protein and fibrinogen levels) parameters in addition to their extensive investigation for vascular risk factors (lipid profile, homocysteine, glucose, EKG, echocardiography...). At baseline and at 3-year follow up, they will also undergo a high resolution B-mode Doppler ultrasound to measure carotid atherosclerosis. All subjects will be re-interviewed every year. Those who report a change in their clinical status suggestive of an outcome event in the period before the 3rd year assessment will be brought in for evaluation. The concurrent measures of local markers of infection and inflammation together with systemic markers of infection and inflammation should help determine which of the infection or the inflammation component of periodontal disease better explains the purported association with atherosclerosis and stroke.